PAULITSCHKE A431 Oct 2014 Supporting Information Table A2. Comparison of keratinocyte-specific proteins (n = 50) versus A431 by number of peptides. *Indicates greater abundance in A431; **similar abundance in the 2 cell types. Accession Name number Keratinocytes A431 Difference (A431keratinocytes) Function In the epidermis, expressed predominantly in the granular layer at apical edge of keratinocytes (at protein level). Upregulated during keratinocyte differentiation. Human Protein Atlas: IHC +++ Upregulated in differentiating keratinocytes. Human Protein Atlas: IHC pending, RNA pos Cross-linked envelope protein of keratinocytes. Human Protein Atlas: IHC+ Human Protein Atlas: IHC: pending, RNA: pos + A. Uniprot A8K2U0 Alpha-2-macroglobulin-like protein 1 39 0 -39 Q6UWP8 Suprabasin 3 0 -3 P35321 Cornifin-A (19 kDa pancornulin) 3 0 -3 P22528 Cornifin-B 3 0 -3 Q92817 Envoplakin 29 12 -17 P58107 Epiplakin (450 kDa epidermal antigen) 65 0 -65 Q15517 Corneodesmosin (S protein) 3 0 -3 P15924 Desmoplakin 55 0 -55 1 Cornified envelope of keratinocytes; may link the cornified envelope to desmosomes and intermediate filaments. Human Protein Atlas: IHC ++ Plakin or cytolinker family. (Epiplakin 1) Human Protein Atlas: IHC: pending, RNA pos Important for epidermal barrier integrity. Found in corneodesmosomes (intercellular structures involved in desquamation). Exclusively expressed in skin. Human Protein Atlas: IHC: pos: Major high molecular weight protein of desmosomes. PAULITSCHKE A431 Oct 2014 Q02487 Desmocollin-2 (Cadherin family member 2) 2 0 -2 Q14574 Desmocollin-3 (Cadherin family member 3; Desmocollin-4; HT-CP) 3 0 -3 Q13751 Laminin subunit beta-3 (Laminin-5 subunit beta; Epiligrin subunit beta;) Laminin subunit gamma-2 (Laminin-5 subunit gamma) Laminin subunit alpha-3 (Epiligrin 170 kDa subunit) 10 2 -8 7 1 -6 17 0 -17 O14896 Interferon regulatory factor 6 (IRF-6) 4 2 -2 Q92876 Kallikrein-6 2 0 -2 P49862 Kallikrein-7 8 0 -8 Q13753 Q16787 2 Involved in organization of desmosomal cadherinplakoglobin complexes into discrete plasma membrane domains and anchoring of intermediate filaments to desmosomes. Human Protein Atlas:IHC: +++: Component of intercellular desmosome junctions: involved in interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) Human Protein Atlas: IHC: + Component of intercellular desmosome junctions. Involved in interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms. Human Protein Atlas: IHC: +++ Binding to cells via a high affinity receptor, laminin is thought to mediate attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Beta 3: Human Protein Atlas: IHC: + Gamma 2: Human Protein Atlas:IHC: nd, RNA pos Alpha 3: Human Protein Atlas: IHC:nd, RNA: pos Probable DNA-binding transcriptional activator. Key determinant of the keratinocyte proliferation-differentiation switch involved in appropriate epidermal development Human Protein Atlas: IHC: pending, RNA: pos Shows activity against amyloid precursor protein, myelin basic protein, gelatin, casein and extracellular matrix proteins such as fibronectin, laminin, vitronectin and collagen. Human Protein Atlas: IHC: pending, RNA: pos May catalyze the degradation of intercellular cohesive structures in the cornified layer in the continuous shedding of PAULITSCHKE A431 Oct 2014 O43240 Kallikrein-10 11 0 -11 Q9P0G3 Kallikrein-14 2 0 -2 Q6E0U4 Dermokine (Epidermis-specific secreted protein SK30/SK89) 2 0 -2 Q9Y446 Plakophilin-3 17 3 -14 Q9NZT1 Calmodulin-like protein 5 (Calmodulin-like skin protein) 6 4 -2 P16144 Integrin beta-4** 7 7 0 P07476 Involucrin 23 0 -23 O95171 Sciellin 7 0 -7 3 cells from the skin surface. Abundantly expressed in the skin/ expressed by keratinocytes in the epidermis. Human Protein Atlas: IHC: ++ Tumour-suppressor role. Human Protein Atlas: IHC: ++ Serine-type endopeptidase with a dual trypsin-like and chymotrypsin-like substrate specificity. May function through desmoglein DSG1 cleavage in epidermal desquamation, a process by which the most superficial corneocytes are shed from skin surface. Human Protein Atlas: IHC: + May act as a soluble regulator of keratinocyte differentiation. Human Protein Atlas: IHC: ++ May play a role in junctional plaques. Found in desmosomes of most simple and stratified epithelia. Human Protein Atlas: IHC: +++ Binds calcium; may be involved in terminal differentiation of keratinocytes. Particularly abundant in the epidermis where its expression is directly related to keratinocyte differentiation. Human Protein Atlas: IHC: ++ Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells; required for regulation of keratinocyte polarity and motility. Human Protein Atlas: IHC: ++ Part of insoluble cornified cell envelope (CE) of stratified squamous epithelia. Keratinocytes of epidermis and other stratified squamous epithelia. Human Protein Atlas: IHC: ++ May function in assembly/regulation of proteins in cornified envelope. Highly expressed in esophagus; also expressed in PAULITSCHKE A431 Oct 2014 P03973 Antileukoproteinase 3 0 -3 P25815 Protein S100-P 10 2 -8 P29034 Protein S100-A2 5 2 -3 P19957 Elafin (Elastase-specific inhibitor) 3 0 -3 P22735 Protein-glutamine gamma-glutamyltransferase K (Epidermal TGase) 4 0 -4 keratinocytes, amniotic tissue, foreskin stratum spinosum and stratum granulosum, hair follicle and nail. Human Protein Atlas: IHC: ++ Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues. Human Protein Atlas: IHC:nd, RNA: pos May stimulate cell proliferation in an autocrine manner via activation of the receptor for activated glycation end products Human Protein Atlas: IHC:nd, RNA: pos May play a role in suppressing tumour cell growth; expressed by a subset of epithelial cells including normal human mammary epithelial cells and keratinocytes. Human Protein Atlas: IHC: ++ Neutrophil and pancreatic elastase-specific inhibitor of skin; may prevent elastase-mediated tissue proteolysis Human Protein Atlas: IHC: +++ Responsible for cross-linking epidermal proteins during formation of the stratum corneum. Human Protein Atlas: IHC: ++ B. Pubmed P10645 Chromogranin-A (CgA) 2 0 -2 Q5VT79 Annexin A8-like protein 2* 5 8 3 P13928 Annexin A8* 5 9 4 4 Pancreastatin strongly inhibits glucose induced insulin release from the pancreas. Associated with the secretory granule membrane to SCG3, that in turn binds to cholesterolenriched lipid rafts in intragranular conditions Human Protein Atlas: IHC:nd, RNA: pos A pair of annexin repeats may form one binding site for calcium and phospholipid. Human Protein Atlas: IHC: pending, RNA: pos Anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. PAULITSCHKE A431 Oct 2014 Human Protein Atlas: IHC: pending, RNA: pos P36952 Serpin B5 (Peptidase inhibitor 5) 21 5 -16 O95633 Follistatin-related protein 3 3 0 -3 O00204 Sulfotransferase family cytosolic 2B member 1 10 0 -10 O95757 Heat shock 70 kDa protein 4L 9 0 -9 Q9HCY8 Protein S100-A14 7 4 -3 P51178 1-phosphatidylinositol-4,5bisphosphate phosphodiesterase delta-1 7 0 -7 Q14116 Interleukin-18 4 1 -3 Q96QA5 Gasdermin-A 7 0 -7 Q9H1E1 Ribonuclease 7 10 0 -10 5 Tumour suppressor; blocks growth, invasion, and metastatic properties of mammary tumours Human Protein Atlas: IHC: +++ Involved in bone formation; inhibits osteoclast differentiation. Involved in hematopoiesis; involved in differentiation of hematopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin Human Protein Atlas: IHC: ++ Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but can also result in bioactivation to form active metabolites. Human Protein Atlas: IHC: +++ Chaperone activity in vitro; inhibits aggregation of citrate synthase Human Protein Atlas: IHC: + Involved in Ca ion binding and cell junction. Human Protein Atlas: IHC: +++ Production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. Human Protein Atlas: IHC: + Augments natural killer cell activity in spleen cells, stimulates interferon gamma production in TH-1 cells. Human Protein Atlas: IHC: + Found predominantly in the gastrointestinal tract and to a lesser extent in skin. Human Protein Atlas: IHC: ++ Skin-derived antimicrobial protein 2. Exhibits a potent RNase activity; broad-spectrum antimicrobial activity against PAULITSCHKE A431 Oct 2014 P12532 Creatine kinase U-type, mitochondrial* 10 11 1 P09758 Tumour-associated calcium signal transducer 2 3 2 -1 many pathogenic microorganisms also in skin. Human Protein Atlas: IHC: ++ Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues such as skeletal muscle, heart, brain Human Protein Atlas: IHC: +++ May function as a growth factor receptor. Human Protein Atlas: IHC: ++ C. New candidates Q8TE68 Epidermal growth factor receptor kinase substrate 8-like protein 1 6 0 -6 Q9UQB8 Brain-specific angiogenesis inhibitor 1-associated protein 2 7 1 -6 O15231 Zinc finger protein 185 6 0 -6 Q9BW04 Specifically androgen-regulated gene protein 4 0 -4 P11137 Microtubule-associated protein 2 (MAP-2) 4 0 -4 6 Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton. Human Protein Atlas: IHC: ++ Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42mediated reorganization of the actin cytoskeleton and RAC1mediated membrane ruffling. Involved in regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Human Protein Atlas: IHC: ++ May be involved in regulation of cellular proliferation and/or differentiation. Human Protein Atlas: IHC: +++ Putative androgen-specific receptor. Human Protein Atlas: IHC: ++ Exact function of MAP2 unknown but MAPs may stabilize the microtubules against depolymerisation; also seem to have a stiffening effect on microtubules. Human Protein Atlas: IHC:nd, RNA: pos PAULITSCHKE A431 Oct 2014 Q5K651 Sterile alpha motif domain-containing protein 9 (SAM domain-containing protein 9)** 7 8 1 Q4G0N8 Sodium/hydrogen exchanger 10 (Na(+)/H(+) exchanger 10, Spermspecific Na(+)/H(+) exchanger;sNHE) 3 0 -3 7 May play a role in the inflammatory response to tissue injury and control of extraosseous calcification, acting as a downstream target of TNF-alpha signaling. Human Protein Atlas: IHC: ++ Required for the expression and bicarbonate regulation of the soluble adenylyl cyclase (sAC) Human Protein Atlas: IHC:nd, RNA: pos PAULITSCHKE A431 Oct 2014 Table A3. Inflammatory profile in A431: proteins common to keratinocytes stimulated with IL-1 beta (but not present in normal keratinocytes) and A431 cells (n = 49). Accession number Name Peptides Function Category by GO terms O00161 Synaptosomal-associated protein 23 (SNAP23;Vesicle-membrane fusion protein SNAP-23) 1 Cell adhesion O00625 Pirin 3 O14561 Acyl carrier protein, mitochondrial (ACP;NADHubiquinone oxidoreductase 9.6 kDa subunit;CISDAP) Deoxyribonucleoside 5'-monophosphate Nglycosidase (c-Myc-responsive protein Rcl) 2 Essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion Possible transcriptional coregulator. May: contribute to the regulation of cellular processes via its interaction with BCL3; be required for efficient terminal myeloid maturation of hematopoietic cells; play a role in regulation of cell migration; promote apoptosis when overexpressed. Carrier of the growing fatty acid chain in fatty acid biosynthesis in mitochondria. Acyl-protein thioesterase 2 (Lysophospholipase II;LPL-I) Catalase 2 Keratin, type I cytoskeletal 18 (Cytokeratin18;CK-18;Keratin-18;K18;Cell proliferationinducing gene 46 protein) Cytochrome c1, heme protein, mitochondrial (Ubiquinol-cytochrome-c reductase complex cytochrome c1 subunit;Cytochrome c1;Cytochrome b-c1 complex subunit 4) 2 O43598 O95372 P04040 P05783 P08574 8 3 2 2 Transcription, Oxireductase Transport, Lipid Metabolism Catalyzes cleavage of the N-glycosidic bond of Nucleotide deoxyribonucleoside 5'-monophosphates to yield deoxyribose Metabolism 5-phosphate and a purine or pyrimidine base. May hydrolyze fatty acids from S-acylated cysteine residues in Lipid proteins such as trimeric G alpha proteins or HRAS. Metabolism Occurs in almost all aerobically respiring organisms, protects Oxireductase cells from toxic effects of hydrogen peroxide. Promotes growth of cells including T-cells, B-cells, myeloid leukemia, melanoma and mastocytoma cells and normal and transformed fibroblasts. Together with KRT8 is involved in interleukin-6 (IL-6)- Intermediate mediated barrier protection. Filament Heme-containing component of the cytochrome b-c1 complex, Cell junction, which accepts electrons from Rieske protein and transfers Electron electrons to cytochrome c in the mitochondrial respiratory transport chain. PAULITSCHKE A431 Oct 2014 P11177 Pyruvate dehydrogenase E1 component subunit beta, mitochondrial (PDHE1-B) 2 P17980 26S protease regulatory subunit 6A (Proteasome 26S subunit ATPase 3;TAT-binding protein 1;TBP-1;Proteasome subunit P50) Glutathione S-transferase Mu 3 (GSTM3-3;GST class-mu 3;hGSTM3-3) 2 P24844 Myosin regulatory light polypeptide 9 (Myosin regulatory light chain 9;Myosin regulatory light chain MRLC1) 5 P28838 Cytosol aminopeptidase (Leucine aminopeptidase; Peptidase S) 3-hydroxyisobutyrate dehydrogenase, mitochondrial (HIBADH) 1 P21266 P31937 2 3 P33316 Deoxyuridine 5'-triphosphate nucleotidohydrolase, 4 mitochondrial (dUTPase;dUTP pyrophosphatase) P33992 DNA replication licensing factor MCM5 (CDC46 homolog;P1-CDC46) 2 P36639 7,8-dihydro-8-oxoguanine triphosphatase (8-oxodGTPase; Nucleoside diphosphate-linked moiety X motif 1; Nudix motif 1) Nuclear pore glycoprotein p62 (Nucleoporin Nup62; 62 kDa nucleoporin) 1 P37198 9 3 The pyruvate dehydrogenase complex catalyzes overall conversion of pyruvate to acetyl-CoA and CO2, and thereby links the glycolytic pathway to the tricarboxylic cycle. The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. Carbohydrate and Glucose metabolism ATP/nucleotide binding Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May govern uptake and detoxification of both endogenous compounds and xenobiotics at the testis and brain blood barriers Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation. Implicated in cytokinesis, receptor capping, and cell locomotion. Presumably involved in the processing and regular turnover of intracellular proteins. 3-hydroxy-2-methylpropanoate + NAD+ = 2-methyl-3oxopropanoate + NADH Detoxification Ca ion binding, Splicing, Axon guidance Proteolysis Branched-chain amino acid catabolism Enzyme involved in nucleotide metabolism: produces dUMP, Nucleotide the immediate precursor of thymidine nucleotides, and metabolism decreases intracellular dUTP levels so that uracil cannot be incorporated into DNA. Acts as component of the MCM2-7 complex (MCM complex), DNA binding, the putative replicative helicase essential for 'once per cell DNA cycle' DNA replication initiation and elongation in eukaryotic replication, cell cells. cycle Antimutagenic. Acts as a sanitizing enzyme for oxidized DNA repair nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress. Essential component of the nuclear pore complex. The N- Protein terminal is probably involved in nucleocytoplasmic transport. transport, NFkappaB signalling PAULITSCHKE A431 Oct 2014 P49321 Nuclear autoantigenic sperm protein (NASP) 2 P51970 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 (NADH-ubiquinone oxidoreductase 19 kDa subunit; Complex I-19kD; CI-19kD; Complex I-PGIV; CI-PGIV) 1 P54920 Alpha-soluble NSF attachment protein (SNAPalpha; N-ethylmaleimide-sensitive factor attachment protein alpha) Ubiquitin-conjugating enzyme E2 D2 (Ubiquitinprotein ligase D2; Ubiquitin carrier protein D2; Ubiquitin-conjugating enzyme E2-17 kDa 2; E2(17)KB 2) 5 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (Transducin beta chain 2; G protein subunit beta-2) Nucleobindin-1 (CALNUC) 4 39S ribosomal protein L49, mitochondrial (L49mt;Protein NOF1; Neighbor of FAU; NOF) Splicing factor 3B subunit 2 (Pre-mRNA-splicing factor SF3b 145 kDa subunit; SF3b145; SF3b150; Spliceosome-associated protein 145; SAP 145) Phosphomevalonate kinase (PMKase) 1 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HCDH;) 3 P62837 P62879 Q02818 Q13405 Q13435 Q15126 Q16836 10 2 1 5 1 Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. Cellcycle, DNA replication, Transport, Chromatin remodeling Accessory subunit of the mitochondrial membrane respiratory Mitochondrial chain NADH dehydrogenase (Complex I), that is believed not electron to be involved in catalysis. transport, NADH dehydrogenase activity Required for vesicular transport between the endoplasmic Transport reticulum and Golgi apparatus. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. Major calcium-binding protein of the Golgi. May have a role in calcium homeostasis Structual constituent of ribosome Ubiquitinconjugationpathway, ATP/ nucleotide binding GTPase activity DNA binding, Ca ion binding Translation Subunit of the splicing factor SF3B required for 'A' complex mRNA splicing assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. ATP + (R)-5-phosphomevalonate = ADP + (R)-5- Lipid diphosphomevalonate. Metabolism, ATP binding Plays an essential role in the mitochondrial beta-oxidation of Lipid short chain fatty acids. Metabolism, NAD binding PAULITSCHKE A431 Oct 2014 Q16891 Mitochondrial inner membrane protein (Mitofilin; p87/89; Cell proliferation-inducing gene 4 protein) Epithelial splicing regulatory protein 1 (RNAbinding motif protein 35A; RNA-binding protein 35A) 1 Q7L014 Probable ATP-dependent RNA helicase DDX46 (DEAD box protein 46; PRP5 homolog) 6 Q86VI1 Exocyst complex component 3-like protein (Protein Jiangli) 39S ribosomal protein L50, mitochondrial (L50mt) Sulfatase-modifying factor 2 (C-alphaformylglycine-generating enzyme 2) 1 Q8TEQ6 Gem-associated protein 5 (Gemin5) 1 Q92734 Protein TFG (TRK-fused gene protein) 1 Q92878 DNA repair protein RAD50 (hRAD50) 1 Q96CV9 Optineurin (Optic neuropathy-inducing protein;NEMO-related protein;Transcription factor IIIA-interacting protein;TFIIIA-IntP) 1 Q6NXG1 Q8N5N7 Q8NBJ7 11 1 1 3 Interacts with OPA1, preferentially with the soluble OPA1 form. Mitochondrial calcium ion homeostasis mRNA splicing factor that regulates the formation of epithelial mRNA cell-specific isoforms. Specifically regulates the expression of processing and FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. splicing Regulates changes in splicing during the epithelial-tomesenchymal transition (EMT) Plays an essential role in splicing, either prior to, or during mRNA splicing A complex formation. processing and splicing, ATP binding As part of the exocyst, may play a role in regulated exocytosis Exocytosis of insulin granules Mitochondrion. Mitochondrion Lacks formyl-glycine generating activity and is unable to Postconvert newly synthesized inactive sulfatases to their active translational form. protein modification The SMN complex plays an essential role in spliceosomal mRNA snRNP assembly in the cytoplasm and is required for pre- processing and mRNA splicing in the nucleus. splicing May be involved in pathogenesis of thyroid papillary NF-kappa B carcinoma. signalling Component of the MRN complex, which plays a central role in Cell cycle, double-strand break (DSB) repair, DNA recombination, DNA maintenance of telomere integrity and meiosis. The complex damage/repair, possesses single-strand endonuclease activity and double- ATP binding strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. Plays an important role in the maintenance of the Golgi Cell cycle complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. PAULITSCHKE A431 Oct 2014 Q96DE0 U8 snoRNA-decapping enzyme (Nucleoside diphosphate-linked moiety X motif 16;Nudix motif 16;U8 snoRNA-binding protein H29K) DAZ-associated protein 1 (Deleted in azoospermia-associated protein 1) Endoplasmic reticulum resident protein ERp44 (Thioredoxin domain-containing protein 4) 1 Q9BX68 Histidine triad nucleotide-binding protein 2 (HINT-2;HINT-3; PKCI-1-related HIT protein) 2 Q9NRV9 Heme-binding protein 1 (p22HBP) 1 Q9NRX2 39S ribosomal protein L17, mitochondrial (L17mt;LYST-interacting protein 2) Methionine adenosyltransferase 2 subunit beta (Methionine adenosyltransferase II beta;MAT II beta; DTDP-4-keto-6-deoxy-D-glucose 4reductase) Glyoxylate reductase/hydroxypyruvate reductase 1 Q9UHY7 Enolase-phosphatase E1 (2,3-diketo-5-methylthio1-phosphopentane phosphatase;MASA homolog) 2 Q9UIJ7 GTP:AMP phosphotransferase mitochondrial (Adenylate kinase 3;AK 3) TP53RK-binding protein (PRPK-binding protein) 2 Q96EP5 Q9BS26 Q9NZL9 Q9UBQ7 Q9Y3C4 12 2 1 1 4 1 RNA-binding and decapping enzyme that catalyzes the Nucleotide cleavage of the cap structure of snoRNAs and mRNAs in a metabolism metal-dependent manner. RNA-binding protein RNA/nucleotid e binding Mediates thiol-dependent retention in the early secretory Stress response pathway. Inhibits the calcium channel activity of ITPR1. May have a role in the control of oxidative protein folding in the endoplasmic reticulum. Hydrolase probably involved in steroid biosynthesis. May play Lipid a role in apoptosis. Metabolism, Apoptosis May bind free porphyrinogens that may be present in the cell Heme binding and thus facilitate removal of these potentially toxic compounds. Binds with a high affinity to one molecule of heme or porphyrins. Mitochondrion Mitochondrion Non-catalytic regulatory subunit of S-adenosylmethionine synthetase 2 (MAT2A). Its expression in hepatoma cell lines may lead to increase DNA synthesis and thereby participate in cell proliferation. Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities Bifunctional enzyme One carbon metabolism Oxireductase Amino acid / Methionine biosynthesis Involved in maintaining the homeostasis of cellular nucleotides Nucleotide by catalyzing the interconversion of nucleoside phosphates. binding Interacts with TP53RK/PRPK. Protein catabolic process.